The re-emergence of resistant cancer cells after initial therapy is one of the great unsolved, and deadly, problems in oncology, and a fundamental problem of evolution under stress. This project is aimed at understanding, from general principles of physics, ecology, and biology, why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. We believe that evolution in small, stressed habitats is the key to the rapid and inevitable re-emergence of resistance. The physical technology that drives this Project uses microfabrication of tiny, stressed habitats to test these Ideas. Modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.